ANGIOTENSIN II FOR CATECHOLAMINE-RESISTANT VASODILATORY SHOCK IN PATIENTS WITH ACUTE KIDNEY INJURY: A POST HOC ANALYSIS OF THE ATHOS-3 TRIAL.

Objective: The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear. Methods: We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) 3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe.

New drugs on the horizon for acute kidney injury.

Purpose Of Review: Acute kidney injury (AKI) is a frequent and serious complication in critically ill patients. Currently, no effective therapy to prevent or treat AKI is available. This review highlights recently published developments on pharmacological treatments that aim to prevent AKI or to alleviate the severity of AKI in critical ill patients.

Long-term monocyte activation after coronary artery bypass grafting: An exploratory prospective observational study.

Major surgery such as coronary artery bypass grafting (CABG) is associated with an increased post-operative risk of atherosclerotic cardiovascular events. Cells of the innate immune system can adopt a long-lasting pro-inflammatory and atherogenic phenotype after brief exposure to exogenous or endogenous inflammatory stimuli, a process called "trained immunity". We hypothesized that the surgery-induced inflammation leads to sustained alterations in monocyte function, which promote the subsequent occurrence of cardiovascular events.

Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients.

Purpose: Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect.

Methods: We applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022.

Interpretation of results of PCR and B-D-glucan for the diagnosis of Pneumocystis Jirovecii Pneumonia in immunocompromised adults with acute respiratory failure.

Background: The accuracy of a diagnostic test depends on its intrinsic characteristics and the disease incidence. This study aims to depict post-test probability of Pneumocystis pneumonia (PJP), according to results of PCR and Beta-D-Glucan (BDG) tests in patients with acute respiratory failure (ARF).

Materials And Methods: Diagnostic performance of PCR and BDG was extracted from literature.

Preclinical and first-in-human safety studies on a novel magnetism-based haemofiltration method.

Extracorporeal haemofiltration devices that selectively remove cytokines could represent an adjunctive treatment in inflammatory diseases. One such device is the "IL-6-Sieve", wherein magnetic Anti-IL-6 Beads are introduced into an extracorporeal circuit via a Bead Adapter and then removed along with any surface-bound interleukin (IL)-6 by a Filter deployed in a Magnet, before the blood is returned to the patient. We report here on a series of animal studies, and a first-in-human study, on the safety of the IL-6-Sieve.

Impaired angiotensin II signaling in septic shock.

Recent years have seen a resurgence of interest for the renin-angiotensin-aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II-angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin-angiotensin-aldosterone system during septic shock can occur at three distinct levels: 1.

Towards personalized medicine: a scoping review of immunotherapy in sepsis.

Despite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable.

Phosphodiesterase 3 inhibitors do not influence lactate kinetics and clinical outcomes in patients with septic shock: A multicentre cohort study.

Purpose: We investigated the association between the administration of phosphodiesterase 3 inhibitors (PDE3i) and lactate kinetics, resolution of organ failure, ICU and hospital length of stay (LOS) and hospital mortality in a retrospective cohort of patients with septic shock and persistently elevated lactate concentrations.

Material And Methods: Patients with septic shock and two arterial lactate concentrations ≥4 mmol/L with at least 4 h between measurements were eligible. Clinical data of the first four days of admission were collected in an online database.

Neo-epitope detection identifies extracellular matrix turnover in systemic inflammation and sepsis: an exploratory study.

Background: Sepsis is associated with high morbidity and mortality, primarily due to systemic inflammation-induced tissue damage, resulting organ failure, and impaired recovery. Regulated extracellular matrix (ECM) turnover is crucial for maintaining tissue homeostasis in health and in response to disease-related changes in the tissue microenvironment. Conversely, uncontrolled turnover can contribute to tissue damage.

Specific and Non-specific Aspects and Future Challenges of ICU Care Among COVID-19 Patients with Obesity: A Narrative Review.

Purpose Of Review: Since the end of 2019, the coronavirus disease 2019 (COVID-19) pandemic has infected nearly 800 million people and caused almost seven million deaths. Obesity was quickly identified as a risk factor for severe COVID-19, ICU admission, acute respiratory distress syndrome, organ support including mechanical ventilation and prolonged length of stay. The relationship among obesity; COVID-19; and respiratory, thrombotic, and renal complications upon admission to the ICU is unclear.

Sepsis-associated acute kidney injury: recent advances in enrichment strategies, sub-phenotyping and clinical trials.

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI.

Myeloid-Derived Suppressor-like Cells as a Prognostic Marker in Critically Ill Patients: Insights from Experimental Endotoxemia and Intensive Care Patients.

Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections.

Phenotype-specific therapeutic efficacy of ilofotase alfa in patients with sepsis-associated acute kidney injury.

Background: There is no effective treatment for sepsis-associated acute kidney injury (SA-AKI). Ilofotase alfa (human recombinant alkaline phosphatase) has been shown to exert reno-protective properties, although it remains unclear which patients might be most likely to benefit. We aimed to identify a clinical phenotype associated with ilofotase alfa's therapeutic efficacy.

Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL).

Purpose: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety.

Methods: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI.

The pathophysiology of sepsis and precision-medicine-based immunotherapy.

Sepsis remains a major cause of morbidity and mortality in both low- and high-income countries. Antibiotic therapy and supportive care have significantly improved survival following sepsis in the twentieth century, but further progress has been challenging. Immunotherapy trials for sepsis, mainly aimed at suppressing the immune response, from the 1990s and 2000s, have largely failed, in part owing to unresolved patient heterogeneity in the underlying immune disbalance.

Assessing GFR With Proenkephalin.

Introduction: In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Creatinine is recognized as a late and insensitive biomarker of glomerular filtration rate (GFR). The novel biomarker proenkephalin (PENK) may overcome these limitations, but no PENK-based equation for eGFR is currently available.

[Scepticism about a Chinese herbal mixture for sepsis].

While on the one hand the field yearns for an effective treatment for sepsis, on the other hand a there is a sceptical attitude towards positive results. The EXIT-SEP trial showed that treatment with Xuebijing (XBJ), a mixture of 5 Chinese herbs with 162 different components, significantly reduced mortality. This was a multicentric, double-blinded placebo-controlled, adequately powered trial.